Abstract: In vertebrates, βγ-crystallins are mainly expressed in the lens as structural protein, a lot of non-lens βγ-crystallins were also discovered in microbes and mammals, such as Protein S and Absent in Melanoma 1, which act as microbial stress-inducible protective protein in bacterial, participate in epidermis development and has tumor suppression function in mammals, respectively. However, little is known about the biochemical properties, functions and action mechanisms of these non-lens βγ-crystallins in vertebrates. In this paper, we mainly review the research progression of non-lens βγ-crystallins in the protein structure, gene evolution and biological function.